Murine strains expressing the HPRT (Hypoxanthine Phosphoribosyltransferase) A allele have approximately 30-fold higher levels of HPRT activity in erythroid cells than do strains expressing the more common HPRT B allele. Our objective is to determine which fraction of the elevated level of HPRT activity is attributable to: (1) increased catalytic activity of the enzyme; (2) increased synthesis of the enzyme in early erythroid cells; and/or (3) lack of degradation of the enzyme in erythroid cell development. The murine HPRT A and B enzymes will be purified and their maximal specific activities compared. Immunotitration and pulse-chase experiments will be used to compare the rates (and times) of synthesis and degradation of HPRT in erythroid cells of these strains. If, as preliminary results indicate, the elevated levels of HPRT activity result from differences in the rates at which the HPRT A and B enzymes are degraded, we will use the differential sensitivity of the enzymes to the degradative process as a guide for development of an in vitro assay of HPRT degradation. An assay of HPRT degradation may permit identification of factors that control the rate at which HPRT is degraded in mammalian erythroid cells.